Monoclonal antibodies (mAb's) are important tools in research, diagnostics, and therapy. MAb's with suitable specificities can be highly valuable tools for the modulation of cell signaling and have great potential as cancer therapeutics. Typically, mAb's are prepared using hydridoma cell lines. Generation of such mAbs with desired specificity, however, is difficult when the target antigen or epitope is conserved between human and mouse. Another issue complicating the development of therapeutic mAbs is the fact that the successful outcome of the humanization process, generally implemented to reduce the immunogenicity of the rodent protein, cannot be guaranteed. In addition, commercially available mAbs for research are well known to often have serious quality issues, where one batch of the antibody functions quite differently from another batch from the same manufacturer. There is a constant need of good-quality antibodies for biochemical, structural and functional studies.
The ephrin (Eph) receptors have been sought as therapeutic targets in liquid and solid tumors. Eph receptors are a subcategory of receptor tyrosine kinases, and they therefore play vital parts in cell survival and function. Notably, the receptors within the Eph family are also extremely highly conserved between species, generally having only two-three amino acids differences between the human and mouse proteins. In such instances it is virtually impossible to create antibodies using the classical murine technology.
EphA2 is a sensory receptor protein on the surface of both normal and cancerous lymphocytes and is a potential therapeutic target for lymphoma. Inappropriate activation of EphA2 is known to be the cause of follicular and other lymphomas. Follicular lymphoma is a common and incurable form of B-cell lymphoma. Current lymphoma therapeutics show only modest effect against follicular lymphoma and new therapeutics are needed. EphA2 has also been described to be important for the survival in EphA2-positive mouse leukemia models and not essential for normal hematopoiesis. Acute myelogenous leukemia (AML) is another disease with dismal outcomes and thus identification on new therapeutic targets is needed.